Initial studies will be in 3 main areas, (1) studies on the processes involved in host cell-tumor cell interactions; (2) studies on the in vivo correlates of lymphocyte-dependent antibody-mediated cytolysis (LDA) and of cytotoxicity by macrophages; and (3) studies on the tumor cell in the enhanced host and on defects in the host response in enhancement. These will form the basis for the fourth approach, a progressive study of tumors induced in mice of two strains, C57B1/6 and C57B1/10.D2 by Rous Sarcoma Schmidt-Ruppin clone D virus. Lymphocytes from the site of rejection of an ascites tumor bind to, and then lyse, tumor cells in vitro. The dynamic state of the target cell membrane appears to influence binding. To identify the molecules involved in binding, cross-linking agents will be applied to target cells, cytotoxic lymphoid cells, or to the bound combination. Cell fractionation, detergent solubilization, and chromatographic separation of functional lymphocyte and tumor membrane sites will be undertaken to determine their structure. An analysis will be made of the lymphocyte antigen Ka and a comparison made between purified antigens extracted from Rous induced tumors from different mouse strains. LDA activity, standardized in vitro, will be followed in vivo in an adoptive transfer assay system and in diffusion chambers. Alterations in carbohydrate metabolism of enhanced tumor cells will be investigated to determine their mode of initiation and their consequences on cell membrane. LDA activity of serum from enhanced animals and LDA capacity of their lymphoid cells will be measured. The various procedures developed and the information gained in these studies will be mobilized to study immunologic changes in preneoplastic, early, and late tumor-bearing animals. Depending upon the nature of any deficiency found, immunotherapy will be attempted through immunization with purified antigen on a suitable carrier, by sensitizing autologous lymphocytes in vitro or the passive transfer of serum with potent LDA activity.